4-methyl catechol (4-MC) is an endogenous compound occurring in very small concentrations in the human organism, and little is known about the location of formation and regulation of the metabolism in human tissue. It is known, however, that 4-MC may be formed as a metabolite of orally ingested flavonoids such as quercetin and rutin by the activity of the intestinal microbiome in the large intestine of humans.
In vitro investigations and animal studies have described effects of 4-MC that suggest a preventive and/or therapeutic effect for humans. In the following, the different effects and therapeutic applications respectively derived therefrom are described:                1. Anti-inflammatory effects        2. Peroxyl radical and superoxide anion radical scavenging        3 Stimulation of the neurotrophins “Nerve Growth Factor” (NGF), “Brain Derived Nerve Growth Factor” (BDNF), Glial Derived Nerve Growth Factor (GDNF) and others        4 Inhibition of the cholesterol biosynthesis        5 Inhibition of the lipoxygenase        6 Stimulation of the heme oxygenase        7 Inhibition of the “angiotensin converting enzyme” (ACE) activity        
Specific cascade dependencies between these different effects have been described. 4-MC stimulates the phosphoinositol-3-kinase/AKT signal transduction pathway and thereby activates the expression of heme oxygenase, which in turn, also in response to oxidative stress, increases, in addition to iron, the formation of bilirubin and carbon monoxide, which in turn stimulate the expression of the neurotrophins BDNF and GDNF in neurons as well as glial cells (Furukawa, Y. et al., Biomedical Research 2010, 31:45-52; Hung, S. Y. et al., Neuropharmacology 2010 February, 58:321-329).
All effects described above are significant in view of a neuroprotective context and emphasize the role and importance of the intestinal microbial activity.
Peripheral and Autonomic Neuropathies:
To the deuteropathies of diabetes mellitus belongs the diabetic neuropathy, of which 30-50% of the diabetics are affected, and which is thus the most common peripheral neuropathy in the Western countries (Pittenger G., Vinik A., Exp Diabesity Res. 2003 October-December, 4(4):277-85 Review). As a disorder of the peripheral nervous system, it relates to both sensory and motor nerves, and by the heterogeneity, besides the thickly myelinated fibers, also the thinly myelinated fibers are affected. A greatly feared complication being strongly harmful for those affected is the so-called “diabetic foot” (diabetic podopathy). Sensory disorders with and without blood flow disorders will often result in a clinical picture leading to an amputation of the lower limb. Every year in Germany alone, about 30,000 amputations of the lower limb are performed due to this diagnosis (Chantelau E., Deutsches Ärzteblatt 2002, 99:A 2052-2056).
From animal studies on streptozotocin-treated diabetic rats, it is known that the expression of neurotrophins (nerve growth factors) such as “glial cell derived neurotrophic factor” (GDNF), neurotrophin 3, and NGF in the intestines is reduced. This is used to explain the known gastrointestinal complications in diabetic patients (Liu, W. et al., Auton Neurosci. 2010, 154:79-83).
Since the early nineties, it is known that there are a number of compounds that are able to stimulate the endogenous generation of neutrophins (Furukawa Y., et al., Biochem Pharmacol 1990 November 75, 40(10):2337-42). These substances include the alkyl catechols and in particular the 4-MC. For 4-MC it has been shown that neuropathies in various animal models (neuropathies induced by resiniferatoxin, pyridoxine, acrylamide and cytostatics as well as diabetic neuropathy induced by streptozotocin) are favorably influenced by the administration of 4-MC (Hanaoka Y., et al., J Neurol Sci. 1994 March; 122(1):28-32). Similarly, the gentamicin-induced ototoxicity is antagonized by 4-MC via stimulation of NGF and other neurotrophins.
Also in the “crush injury” model of the sciatic nerves of the mouse, MC-4 enhanced the reinnervation of the cutaneous nerves, in particular the non-myelinated nerve fibers (Hsieh, Y. L. et al., J Neuropathol Exp Neurol. 2009; 68:1269-1287).
These results suggest that also in humans, alkyl catechols and their derivatives have preventive and therapeutic effects on various types of neuropathies, as in                diabetic neuropathy, but also in        neuropathy induced by chemotherapy, and        neuropathy as a result of chronic alcohol abuse.Central Nervous Degenerative Diseases:        
In Germany alone, currently more than a million people suffer from dementia, about 700,000 thereof from Alzheimer's disease, a neurodegenerative disease. Every year, approximately 200,000 new dementia diseases are diagnosed, of which about 120,000 are the Alzheimer's type. From Parkinson's disease suffer in Germany currently 300,000-400,000. Due to the demographic trends, the prevalence of both diseases will increase. The financial burdens of the health system caused by these diseases are very high—the treatment and care costs of an Alzheimer's patient today are around 40,000 per year—and will continue to rise. Therapeutic agents for the symptomatic treatment of Parkinson's disease are indeed already available today, and the first products to improve the cognitive functions in patients with Alzheimer's disease show marginal effects, a real breakthrough with agents that stop the progression of these neurodegenerative diseases could however so far not be achieved, despite intensive worldwide research.
The effects of the alkyl catechols and their metabolites indicate a significant therapeutic potential: Besides the already mentioned stimulation of neurotrophins, which also takes place in the central nervous system and counteracts the neurodegeneration process, signal transduction effects have been described, suggesting that by activation of heme oxygenase-1 expression, 4-MC has neuroprotective effects, in particular against the harmful oxidative stress (Furukawa, Y. et al., Biomedical Res 2010, 31:45-52). MC-4 further stimulates the mitogen-activated protein kinase (MAPK/ERK1/2), which in turn activates the “cAMPresponse element binding protein” (CREB). CREB plays an important role for the nerve growth as well as for the survival of the nerve cells.
Oxidative stress is associated with the death of nerve cells and plays a major role in the pathogenesis of many chronic degenerative diseases such as Alzheimer's, Parkinson's, Huntington's chorea and the amyotrophic lateral sclerosis. A signal transduction pathway, in which the transcriptional activation of protective genes is mediated by a “cis-acting element”, the so-called “anti-oxidant responsive element” (ARE), has an increasing importance. Activation by the transcription factor NF-E2-related factor 2 (Nrf2), which binds to ARE, protects nerve cells against cell death induced by oxidative stress (Johnson, J. A., et al., Ann NY Acad. Sci. 2008; 1147:61-69). 4-MC activates Nrf2 and can also act in a neuroprotective manner via this signal transduction pathway (Satoh, T., et al. Biochem Biophys Res Commun. 2009; 379:537-341).
Alkyl catechols such as 4-MC and/or 3,4-dihydroxyphenylacetic acid (another metabolite of rutin) have additional anti-inflammatory properties, which manifest in the inhibition of the expression of the inducible NO synthase and the inhibition of the release of proinflammatory cytokines such as TNF from microglia, therewith clear neuroprotective effects being associated (Zheng, L. T. et al., Eur J Phormacol 2008; 588:106-113). These protective effects can be used to treat neurodegenerative diseases that are associated with marked activation of the microglia.
Maintaining or improving cognitive functions is of great importance for demented patients, e.g. patients with Alzheimer's disease. Indications that alkyl catechols have a positive impact on cognitive performance, result from investigations by Sun, M. K. et al., Neuroreport. 2008; 19:355-359). After intraventricular administration, 4-MC also improved the spatial learning and memory of rats, an effect where apparently BDNF is involved, as simultaneous administration of BDNF antibodies suppressed the effect of 4-MC.
O-methyl metabolites of alkyl catechols, too, such as 2-methoxy-4-ethylphenol have neuroprotective effects that can therapeutically be used in the treatment of degenerative diseases of the central nervous system. They protect nerve cells—as has been shown for hippocampal neurons—against the excessive, neurotoxic influx of calcium ions mediated by NMDA receptors (Fukumori R. et al., J Pharmacol Sci. 2010; 112:273-281).
Hypertension/Atherosclerosis:
In vitro studies on liver cells indicate that not only quercetin, but also 4-MC inhibits the hepatocellular cholesterol synthesis in the μmol region (Glasser G. et al., Phytomedicine 2002, 9:33-40). The inhibition of the angiotensin converting enzyme and other metallopeptidases is described in Bormann, H., et al., Pharmacy. 2000, 55: 129-132.
Diabetes Mellitus:
Inhibition of non-oxidative AGE (advanced glycation end product) formation by 4-MC and DOPAC was shown in Pashikanti, S. et al., Free Radic Biol Med. 2009 Dec. 4.
Osteoporosis:
Metabolites of alkyl catechols such as 2-methoxy-4-methyl phenol (creosol) and 2-methoxy-4-ethylphenol, generated by the catalytic action of catechol-O-methyltransferase, prevent the osteoporosis occurring after ovariectomy of mice—an experimental model of the post-menopausal osteoporosis—probably by inhibition of bone-degrading osteoclasts in conjunction with an anti-oxidative effect on osteoblasts promoting bone growth (Moriguchi N., et al., Biochem Pharmacol 2007, 73:385-393). For hydroxytyrosol (3,4-dihydroxyphenyl-ethanol), too, an appropriate bone-protective effect in ovariectomized rats has been described (Puel C. et al. J Agric Food Chem. 2008; 56: 9417-9422).
Preparations containing ground buckwheat and milk are well known as foods from the practice and from the document JP 2008 271 811 A.
According to this document, buckwheat grains are first subjected to a thermal steam treatment. The milk is not heated before admixture of the buckwheat. From the document Zeller, F. J., et al., Biol. Unserer Zeit, 34th issue 2004, No. 1, pp. 24 ff, it is known to mix normal buckwheat with diluted and heated milk.